IngentaConnect Determination of the Polymorphic Forms of Bicifadine Hydrochlorid...

Authors: McArdle, Patrick¹; Gilligan, Karen¹; Cunningham, Desmond¹; Ryder, Alan²

Source: Applied Spectroscopy, Volume 59, Issue 11, Pages 252A-282A and 1305-1426 (November 2005) , pp. 1365-1371(7)

Publisher: Society for Applied Spectroscopy

Abstract:

The pharmaceutical compound bicifadine hydrochloride, which has been found to crystallize in two polymorphic forms, has been characterized by thermal analysis, X-ray powder diffraction (XRPD), infrared (IR) spectroscopy, and near-infrared (NIR) spectroscopy. A series of 22 sample mixtures of polymorph 1 and polymorph 2 were prepared and calibration models for the quantitation of these binary mixtures have been developed for each of the XRPD, attenuated total reflectance (ATR)-IR, and ATR-NIR analytical techniques. The quantitative results were obtained using a partial least squares (PLS) algorithm, which predicted the concentration of polymorph 1 from the XRPD spectra with a root mean standard error of prediction (RMSEP) of 4.4%, from the IR spectra with a RMSEP of 3.8%, and from the NIR spectra with a RMSEP of 1.4%. The studies indicate that when analyses are carried out on equivalent sets of spectra, NIR spectroscopy offers significant advantages in quantitative accuracy as a tool for the determination of polymorphs in the solid state and is also more convenient to use than both the ATR-IR and XRPD methods. Density functional theory (DFT) B3LYP calculations and IR spectral simulation have been used to determine the nature of the vibrational modes that are the most sensitive in the analysis.

Keywords: POLYMORPHISM; DIFFERENTIAL SCANNING CALORIMETRY; THERMOGRAVIMETRIC ANALYSIS; X-RAY POWDER DIFFRACTION; INFRARED; IR; NEAR INFRARED; NIR; SPECTROSCOPY; ATTENUATED TOTAL REFLECTANCE; ATR; PARTIAL LEAST SQUARES; PLS; QUANTITATIVE; MODELING; SIMULATION

Document Type: Research article

DOI: 10.1366/000370205774783322

Affiliations: 1: Chemistry Department, National University of Ireland, Galway, Ireland 2: National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

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Determination of the Polymorphic Forms of Bicifadine Hydrochloride by Differential Scanning Calorimetry-Thermogravimetric Analysis, X-ray Powder Diffraction, Attenuated Total Reflectance-Infrared Spectroscopy, and Attenuated Total Reflectance-Near-Infrared Spectroscopy